Spontaneity in the patellamide biosynthetic pathway

被引:39
作者
Milne, BF
Long, PF
Starcevic, A
Hranueli, D
Jaspars, M [1 ]
机构
[1] Univ Aberdeen, Marine Nat Prod Lab, Aberdeen AB24 3UE, Scotland
[2] Univ Porto, Ctr Estudos Quim Organ Fitoquim & Farmacol, Fac Farm, P-4050047 Oporto, Portugal
[3] Univ London, Sch Pharm, London WC1N 1AX, England
[4] Univ Zagreb, Fac Food Technol & Biotechnol, Zagreb 10000, Croatia
基金
英国生物技术与生命科学研究理事会;
关键词
D O I
10.1039/b515938e
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Post-translationally modified ribosomal peptides are unusual natural products and many have potent biological activity The biosynthetic processes involved in their formation have been delineated for some, but the patellamides represent a unique group of these metabolites with a combination of a macrocycle, small heterocycles and D-stereocentres. The genes encoding for the patellamides show very low homology to known biosynthetic genes and there appear to be no explicit genes for the macrocyclisation and epimerisation steps. Using a combination of literature data and large-scale molecular dynamics calculations with explicit solvent, we propose that the macrocyclisation and epimerisation steps are spontaneous and interdependent and a feature of the structure of the linear peptide. Our study suggests the steps in the biosynthetic route are heterocyclisation, macrocyclisation, followed by epimerisation and finally dehydrogenation. This study is presented as testable hypothesis based on literature and theoretical data to be verified by future detailed experimental investigations.
引用
收藏
页码:631 / 638
页数:8
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